In-vitro pliability assessment of embolization coils for intracranial aneurysm treatment.

BACKGROUND: Embolization coils have routinely been used to treat intracranial aneurysms via an endovascular approach. Soft coils are typically viewed as the best design for filling and finishing the aneurysms to achieve a higher packing density and are hypothesized to exert a lower force against the aneurysm wall during deployment. We report here an in vitro pliability test method to assess clinically relevant coil softness and compare these metrics for two commercially available framing and finishing coil products. METHODS: A force measurement sensor was affixed onto a side-wall synthetic aneurysm model to continuously measure forces on the aneurysm wall during coil deployment at a fixed delivery rate. A quantitative overall energy metric (average work number or AWN) was calculated from the force-displacement graph representing coil delivery into the aneurysm. Two groups of coils were evaluated: (a) finish coil group (N = 20 ea.): Axium™ Prime Extra Soft coil (ES) and Target™ 360 Nano coil (Nano), and (b) frame coil group (N = 20 ea.): Axium™ Prime FC coil (FC) and Target™ 360 Standard coil (Standard). RESULTS: (a) In the finish coil group, AWN was measured as: ES (0.53 ±â€¯0.09 gf-cm) and Nano (0.99 ±â€¯0.21 gf-cm). (b) In the frame coil group, AWN was measured as FC (2.54 ±â€¯0.53 gf-cm) and Standard (4.48 ±â€¯0.52 gf-cm). In both groups, Axium Prime coils had statistically lower measures of AWN and therefore higher pliability compared to Target coils (p < .001). CONCLUSIONS: The in-vitro pliability test method offers quantitative metrics to assess coil softness during deployment in a clinically relevant aneurysm model.

Thrombogenicity assessment of Pipeline, Pipeline Shield, Derivo and P64 flow diverters in an in vitro pulsatile flow human blood loop model.

Flow diversion is a disruptive technology for the treatment of intracranial aneurysms. However, these intraluminal devices pose a risk for thromboembolic complications despite dual antiplatelet therapy. We report the thrombogenic potential of the following flow diversion devices measured experimentally in a novel human blood in-vitro pulsatile flow loop model: Pipeline™ Flex Embolization Device (Pipeline), Pipeline™ Flex Embolization Device with Shield Technology™ (Pipeline Shield), Derivo Embolization Device (Derivo), and P64 Flow Modulation Device (P64). Thrombin generation (Mean ±â€¯SD; µg/mL) was measured as: Derivo (28 ±â€¯11), P64 (21 ±â€¯4.5), Pipeline (21 ±â€¯6.2), Pipeline Shield (0.6 ±â€¯0.1) and Negative Control (1.5 ±â€¯1.1). Platelet activation (IU/µL) was measured as: Derivo (4.9 ±â€¯0.7), P64 (5.2 ±â€¯0.7), Pipeline (5.5 ±â€¯0.4), Pipeline Shield (0.3 ±â€¯0.1), and Negative Control (0.9 ±â€¯0.7). We found that Pipeline Shield had significantly lower platelet activation and thrombin generation than the other devices tested (p < .05) and this was comparable to the Negative Control (no device, p > .05). High resolution scanning electron microscopy performed on the intraluminal and cross-sectional surfaces of each device showed the lowest accumulation of platelets and fibrin on Pipeline Shield relative to Derivo, P64, and Pipeline. Derivo and P64 also had higher thrombus accumulation at the flared ends. Pipeline device with Phosphorylcholine surface treatment (Pipeline Shield) could mitigate device material related thromboembolic complications.

Thrombogenicity assessment of Pipeline Flex, Pipeline Shield, and FRED flow diverters in an in vitro human blood physiological flow loop model.

Endovascular treatment of intracranial aneurysms with endoluminal flow diverters (single or multiple) has proven to be clinically safe and effective, but is associated with a risk of thromboembolic complications. Recently, a novel biomimetic surface modification with covalently bound phosphorylcholine (Shield Technology™) has shown to reduce the material thrombogenicity of the Pipeline flow diverter. Thrombogenicity of Pipeline Flex, Pipeline Shield, and Flow Redirection Endoluminal Device (FRED) in the presence of human blood under physiological flow conditions-in addition to relative increase in thrombogenicity with multiple devices-remains unknown and was investigated here. Thrombin generation (mean ± SD; µg/mL; thrombin-antithrombin complex or TAT) was measured as FRED (30.3 ± 2.9), Pipeline (13.9 ± 4.4), Pipeline Shield (0.4 ± 0.3), and negative control (no device; 0.1 ± 0.0). Platelet activation (mean ± SD; IU/µL; beta-thromboglobulin or ßTG) was measured as FRED (148 ± 45), Pipeline (92.8 ± 41), Pipeline Shield (16.2 ± 3.5), and negative control (2.70 ± 0.16). FRED was significantly more thrombogenic than Pipeline and Pipeline Shield (p < 0.05) for TAT. Additionally, Pipeline Shield had significantly lower TAT and ßTG than the other devices tested (p < 0.05) and these were comparable to the negative control (p > 0.05). TAT and ßTG scaled proportionately with multiple Pipeline devices (N = 6) but was unaffected by multiple Pipeline Shield (N = 6) devices-the latter being statistically similar to negative control (p > 0.05). © 2018 The Authors. Journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3195-3202, 2018.

In-vitro thrombogenicity assessment of flow diversion and aneurysm bridging devices.

Endoluminal devices such as metallic flow diversion (FD) and aneurysm bridging (AB) stents are used for treatment of intracranial aneurysms. Treatments are associated with thrombogenic events mandating the use of dual antiplatelet therapy in all cases. In the current in vitro study, we utilize a slow binding fluorogenic thrombin specific substrate to measure the thrombin generation potential of six devices: four FD devices (Pipeline™ Flex embolization device, Pipeline™ Flex embolization device with Shield Technology™, SILK+, FRED™) and two AB devices (Solitaire™ AB, LEO+). We show that the Pipeline™ Flex embolization device with Shield Technology™ has significantly lower peak thrombin and takes significantly longer time to achieve peak thrombin (time to peak) compared to the other three FD devices (p < 0.05), with statistically similar results to the less thrombogenic AB devices. We conclude that surface modification of endoluminal stents could be an effective method to mitigate thrombogenic complications.

In-vitro thrombogenicity assessment of polymer filament modified and native platinum embolic coils.

BACKGROUND: Embolic coils have been used to treat intracranial aneurysms using an endovascular approach for more than two decades. However, significant aneurysm recanalization rates have been reported specifically in large and giant aneurysms. Adding filaments to bare Platinum coils is considered a modification and has been proposed to achieve higher aneurysm occlusion rates as compared to bare Platinum coils. Quantitative information - in terms of thrombin generation potential of these modifications - is however lacking. OBJECTIVE: We report here in vitro thrombogenicity of Platinum coils containing Nylon (Axium™ MicroFx™ Nylon coil) and PGLA (Axium™ MicroFx™ PGLA coil) filaments and compare them with equivalent bare Platinum Axium™ coils. METHOD: We utilize a quantitative method that tracks the formation of thrombin upon exposure of the test samples to human platelet rich plasma using a slow binding fluorogenic substrate. RESULTS: We report a significant increase in the total thrombin turnover, the peak thrombin amount and the rate of thrombin generation for the Axium™ MicroFx™ coils and filaments compared to the Axium™ coils and Platinum wire. CONCLUSION: Nylon and PGLA filaments added to bare Platinum coils increase thrombogenicity of coils. This study offers a robust quantitative method to compare thrombus formation efficacy of embolic coils under static conditions.

Selectin-like kinetics and biomechanics promote rapid platelet adhesion in flow: the GPIb(alpha)-vWF tether bond.

The ability of platelets to tether to and translocate on injured vascular endothelium relies on the interaction between the platelet glycoprotein receptor Ib alpha (GPIb(alpha)) and the A1 domain of von Willebrand factor (vWF-A1). To date, limited information exists on the kinetics that govern platelet interactions with vWF in hemodynamic flow. We now report that the GPIb(alpha)-vWF-A1 tether bond displays similar kinetic attributes as the selectins including: 1) the requirement for a critical level of hydrodynamic flow to initiate adhesion, 2) short-lived tethering events at sites of vascular injury in vivo, and 3) a fast intrinsic dissociation rate constant, k(0)(off) (3.45 +/- 0.37 s(-1)). Values for k(off), as determined by pause time analysis of transient capture/release events, were also found to vary exponentially (4.2 +/- 0.8 s(-1) to 7.3 +/- 0.4 s(-1)) as a function of the force applied to the bond (from 36 to 217 pN). The biological importance of rapid bond dissociation in platelet adhesion is demonstrated by kinetic characterization of the A1 domain mutation, I546V that is associated with type 2B von Willebrand disease (vWD), a bleeding disorder that is due to the spontaneous binding of plasma vWF to circulating platelets. This mutation resulted in a loss of the shear threshold phenomenon, a approximately sixfold reduction in k(off), but no significant alteration in the ability of the tether bond to resist shear-induced forces. Thus, flow dependent adhesion and rapid and force-dependent kinetic properties are the predominant features of the GPIb(alpha)-vWF-A1 tether bond that in part may explain the preferential binding of platelets to vWF at sites of vascular injury, the lack of spontaneous platelet aggregation in circulating blood, and a mechanism to limit thrombus formation.